Hatice Elmas

Background and aim: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a well-established minimally invasive method for evaluating pancreatic and biliary tract lesions. Cytological assessment of EUS-FNA samples provides information on the heterogeneous spectrum of pancreatobiliary diseases. This study aimed to describe the real-world diagnostic spectrum, cytomorphological characteristics, specimen adequacy, and distribution of cytological diagnostic categories in pancreatobiliary EUS-FNA specimens obtained in routine clinical practice. Methods: This retrospective real-world diagnostic spectrum study analyzed 1,641 EUS-FNA specimens obtained from pancreatic and biliary tract lesions between January 2021 and November 2025. Specimens were obtained from EUS-FNA procedures performed at 14 referring hospitals across Germany and interpreted at a single central reference cytopathology laboratory. Specimens were processed using conventional May–Grünwald–Giemsa and Papanicolaou staining, and cytological diagnoses were categorized following systematic cytomorphological evaluation with integration of available clinical and radiological information. The primary study outcomes were the distribution of cytological diagnoses, specimen adequacy, non-diagnostic rates, and the cytomorphological spectrum of pancreatobiliary lesions. Because systematic histopathological or long-term clinical reference-standard follow-up was not available for the entire cohort, formal diagnostic performance analyses were not performed. Results: Definitive cytological diagnoses were obtained in 503 cases (30.7%). Non-diagnostic specimens accounted for 133 of 1,641 cases (8.1%), corresponding to a diagnostic yield of 91.9% (1,508/1,641) when all other categories were counted as clinically informative. Pancreatic ductal adenocarcinoma was the most common diagnosis ( n = 291; 17.7%), followed by pancreatic neuroendocrine neoplasms ( n = 51; 3.1%), neuroendocrine carcinoma ( n = 11; 0.7%), acinar cell carcinoma ( n = 10; 0.6%), solid pseudopapillary neoplasm ( n = 6; 0.4%), adenosquamous carcinoma ( n = 2; 0.1%), and mucinous neoplasms including cystadenocarcinoma ( n = 1; 0.1%). Benign and premalignant cystic lesions included pseudocysts ( n = 79; 4.8%), intraductal papillary mucinous neoplasms ( n = 36; 2.2%), and serous cystadenomas ( n = 3; 0.2%). Other findings comprised metastatic tumors ( n = 34; 2.1%), malignant tumors not otherwise specified ( n = 47; 2.9%), suspicious for malignancy ( n = 115; 7.0%), inflammatory lesions ( n = 149; 9.1%), negative/normal cytology ( n = 558; 34.0%), and non-diagnostic samples ( n = 133; 8.1%). Conclusion: EUS-FNA cytology provides clinically relevant information across a wide range of pancreatic and biliary tract lesions. This large, real-world cohort delineates the contemporary diagnostic spectrum of pancreatobiliary EUS-FNA cytology encountered in routine clinical practice and provides reference data on the distribution of cytological diagnostic categories, with a supplementary reclassification according to the WHO International System for Reporting Pancreaticobiliary Cytopathology. These data may serve as reference values for institutional quality assurance, including the monitoring of diagnostic yield and non-diagnostic rates.

Background: Whole‐slide imaging (WSI) is increasingly incorporated into digital cervical cytology workflows; however, interpretive variability in borderline and low‐grade squamous lesions remains a recognized diagnostic challenge. This study evaluated interobserver agreement among cytotechnologists in WSI‐based cervical cytology, focusing on borderline and low‐grade squamous lesions. Methods: Sixty‐eight cervical cytology cases (31 ASC‐US, 19 NILM, 18 LSIL) were independently assessed by 19 cytotechnologists across two WSI‐based evaluation rounds. One participant was excluded due to incomplete evaluations in Round 1. Interobserver agreement was evaluated using Fleiss' kappa, Kendall's W , intraclass correlation coefficient, Krippendorff's alpha, Cronbach's alpha and Spearman rank correlation. Conclusions: Digital assessment using WSI demonstrated moderate interobserver agreement among cytotechnologists, with the greatest variability observed in ASC‐US cases. Repeated evaluation was associated with high internal consistency. Findings are compatible with interpretive variability; WSI‐specific effects cannot be excluded without a direct comparator. Paired rater medians did not differ significantly (4.38 vs. 4.00 min; p = 0.090).

Background: Digital imaging in cytopathology is transforming information exchange and remote diagnostics. Internet-based platforms and algorithms are increasingly expected to support cyto‑ and histopathological reporting workflows. This study evaluated interobserver concordance, diagnostic accuracy, causes of misdiagnosis, scanning time, and review time among ten expert cytologists using whole slide imaging (WSI). The primary aim was to identify challenges in applying WSI to cytopathology and to propose strategies to address them. Methods: This retrospective study included 61 intraoperative pulmonary cytology samples (30 women, 31 men; mean age 66.1 years) from the LungenClinic Grosshansdorf acquired between January 2020 and December 2021. A total of 61 Giemsa‑stained preparations (54 imprint/touch preparations, five fine‑needle aspirates, and two sediment smears of pleural effusions) were scanned using a Leica Aperio AT2 scanner and uploaded to an internet platform. Histology served as the reference standard and showed 19 benign and 42 malignant lesions. Results: Sixty‑one cytological cases (19 benign, 42 malignant) were assessed by ten observers. Interobserver agreement for categorical diagnoses was slight (Fleiss' kappa = 0.099), whereas ranking concordance was moderate (Kendall's tau = 0.314). Evaluation times ranged from 20 to 667.8 seconds per case, indicating substantial variability in digital navigation speed. Conclusions: WSI enables international collaboration and remote review of pulmonary cytology, but substantial variability persists in observer interpretations. WSI is currently feasible mainly for consultation, education, and quality assurance, but it is not yet equivalent to conventional microscopy for primary diagnostics, underlining the need for workflow optimization, cytology‑specific validation, and structured digital training.

Background: Bronchoalveolar lavage (BAL) is an important adjunctive tool in the multidisciplinary evaluation of interstitial lung diseases (ILDs), particularly hypersensitivity pneumonitis (HP) and nonspecific interstitial pneumonia (NSIP). However, considerable overlap in BAL cellular profiles and inconsistent lymphocyte thresholds limit its independent diagnostic value. This systematic review summarizes current evidence regarding the diagnostic and prognostic utility of BAL cellular analysis in differentiating HP from NSIP. Methods: A systematic literature search of PubMed/MEDLINE, Embase, CENTRAL identified studies evaluating BAL cellular, immunophenotypic, and biomarker findings in HP and NSIP. Study selection followed PRISMA recommendations. Owing to methodological heterogeneity, the evidence was synthesized narratively. Results: Twenty-one studies met the inclusion criteria. BAL lymphocytosis consistently supported the diagnosis of HP, particularly at thresholds above 30%, although higher cut-offs improved specificity at the expense of sensitivity. Considerable overlap between HP and NSIP was observed, especially in fibrotic disease, limiting the diagnostic performance of isolated lymphocyte percentages. Emerging BAL biomarkers, including CD4/CD8 ratio, NK/NKT-cell subsets, IL-9 signaling, KL-6, and flow cytometric immunophenotyping, showed potential to improve differential diagnosis. In addition, higher BAL lymphocyte counts were associated with favorable treatment response and improved prognosis in selected HP and NSIP populations. Conclusion: BAL cellular analysis remains a valuable complementary diagnostic tool rather than a standalone test for distinguishing HP from NSIP. Accurate interpretation requires integration with exposure history, high-resolution computed tomography, histopathology when available, and multidisciplinary discussion. Standardized BAL protocols and prospective validation of advanced immunophenotypic biomarkers are needed to improve diagnostic precision and clinical decision-making in fibrotic ILDs. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261397405 , identifier PROSPERO (CRD420261397405).

Background: Whole slide imaging (WSI) has emerged as a key component of digital pathology, enabling remote diagnostics and standardized evaluation. However, its diagnostic concordance in thyroid cytopathology, particularly under real-world conditions, remains insufficiently validated. Methods: In this retrospective pilot study, thirteen thyroid cases were evaluated using both conventional light microscopy and WSI. One pathologist performed glass slide evaluation, while two independent pathologists assessed the corresponding digital slides remotely. All evaluations were conducted in a blinded manner. Diagnostic agreement was analyzed using percentage concordance and Cohen’s kappa coefficient. Results: The overall concordance rate between conventional microscopy and WSI was 69.2%. Cohen’s kappa values ranged from 0.58 to 0.63, indicating moderate to substantial agreement. Full concordance was observed in 7 cases, predominantly among malignant diagnoses. Partial concordance occurred in 5 cases, mainly involving borderline categories. Complete discordance was identified in 1 case, exclusively within an indeterminate cytological category. No clinically significant misclassification between benign and malignant diagnoses was observed. Conclusion: WSI demonstrated moderate diagnostic agreement with conventional microscopy in well-defined thyroid cytopathology categories. However, variability remains more pronounced in indeterminate cases, reflecting inherent diagnostic challenges. These findings support the preliminary feasibility of WSI in real-world and remote diagnostic workflows, although larger, multicenter studies are required to confirm these results.

Amaç: PD-L1 immünohistokimyası (IHC), küçük hücreli dışı akciğer kanseri (KHDAK) olan bireylerde immün kontrol noktası inhibitörü (ICI) tedavisini yönlendiren temel bir prediktif biyobelirteç testidir. Ancak antikor klonlarındaki, derecelendirme sistemlerindeki (Tümör Oranı Skoru (TPS), Kombine Pozitif Skor (CPS), İmmün Hücre skoru (IC)) ve pre-analitik/analitik koşullardaki değişkenlik, özellikle KHDAK'ta küçük biyopsiler ve sitolojik örneklerde yorumlamayı ve tekrarlanabilirliği zorlaştırmaktadır. Bu derlemede, tümör heterojenliği, sitolojik kısıtlılıklar ve yapay zekâ (AI) tabanlı dijital patoloji araçlarının gelişen rolü vurgulanarak, KHDAK’ta PD-L1 testindeki güncel uygulamaları, zorlukları ve gelişmeleri gözden geçirmek amaçlanmıştır. Ayrıca radyomiklerin de dahil olduğu multimodal yaklaşımların doku temelli değerlendirmeyi nasıl tamamlayabileceğini ve ICI tedavisi için hasta seçiminde iyileşme sağlayıp sağlayamayacağını incelemeyi hedefledik. Gereç ve Yöntemler: Ocak 2020 ile Haziran 2025 arasında yayımlanmış çalışmalar taranarak, KHDAK’ta PD-L1 ekspresyonunu doğrulanmış klonlar (22C3, 28-8, SP263, SP142), sitoloji–histoloji uyumu, pre-analitik faktörler ve AI tabanlı PD-L1 skorlama platformları ile değerlendiren çalışmalar üzerine kapsamlı bir literatür taraması yapıldı. Veriler, teknik değişkenlikleri, yorumlayıcı farklılıkları ve ortaya çıkan dijital çözümleri ele alan tematik bir sentez ile analiz edildi. Bulgular: KHDAK’ta PD-L1 ekspresyonu, mekânsal heterojenite ve teknik değişkenliklerden etkilenmekte olup tanısal tutarsızlığa yol açmaktadır. Sitolojik örnekler, sınırlı mimari yapı ve fiksasyon artefaktları nedeniyle benzersiz zorluklar oluşturur. Gözlemciler arası değişkenlik, özellikle %1–49 TPS aralığında en yüksektir. AI destekli algoritmalar ve dijital platformlar, iyileştirilmiş tekrarlanabilirlik (κ 0.74’e kadar), doğruluk (%95’e kadar) ve klinik sonuçlarla olası korelasyon göstermiştir. Lunit SCOPE PD-L1 ve HALO Lung PD-L1 AI gibi ticari AI platformları, %92’ye varan doğruluk oranı elde etmiş ve sınırda sonuçlardaki yanlış sınıflandırma oranlarını %18–30 azaltmıştır. PET tabanlı görüntüleme kullanan radyomikler—SUVmax, metabolik tümör hacmi ve heterojenlik indekslerini içeren—özellikle doku örneklemesinin sınırlı olduğu durumlarda invaziv olmayan bir tamamlayıcı yöntem olarak umut vadetmektedir. Sonuç: Güvenilir PD-L1 testi, klonlara özgü validasyon, standart protokollere uyum ve örnek sınırlılıklarının farkında olunmasını gerektirir. AI tabanlı dijital patoloji ve radyomiklerin entegrasyonu, özellikle belirsiz veya sınırlı örneklerde tanısal doğruluğu artırabilir.

Introduction: Spindle cell lesions in the head and neck often mimic sarcomas but may include a wide range of benign and malignant entities. Fine-needle aspiration (FNA) is a minimally invasive method used to evaluate such lesions, though cytological interpretation can be challenging due to overlapping features. Methods: This retrospective study included 12 primary spindle cell lesions of the head and neck, selected based on inclusion/exclusion criteria. Papanicolaou and May-Grünwald-Giemsa stains were used for smear evaluation. Cell blocks were prepared, and cytological diagnoses were compared with histopathological outcomes. Results: The 12 cases were diagnosed as follows: nodular fasciitis (n = 2), schwannoma (n = 2), malignant peripheral nerve sheath tumor (n = 1), leiomyosarcoma (n = 1), liposarcoma (n = 1), rhabdomyosarcoma (n = 1), osteosarcoma (n = 3), and chondroblastoma (n = 1). Cytological features showed moderate correlation with final histology. Conclusion: FNA is a valuable, cost-effective tool for evaluating spindle cell lesions in the head and neck. While morphological overlap poses diagnostic limitations, ancillary techniques and molecular studies enhance its accuracy and clinical utility.

Lung cancer is a highly heterogeneous disease that presents significant challenges in accurate diagnosis and classification due to its diverse histological and molecular characteristics. Traditional diagnostic methods, while valuable, are often limited by invasiveness, subjectivity, and an inability to fully capture tumor complexity. Recent advancements in artificial intelligence (AI), machine learning, and radiomics have transformed the field, offering enhanced precision, efficiency, and objectivity in lung cancer classification. These technologies enable detailed analyses of imaging data, histopathological findings, and molecular profiles, facilitating improved subtype identification, outcome prediction, and personalized treatment strategies. Cytopathology remains a cornerstone of lung cancer diagnostics, particularly for small biopsies and cytological samples, which are often the only materials available in advanced stages. The integration of AI-driven methods into cytopathology and radiomics workflows has shown substantial potential to overcome the limitations of traditional approaches, reduce interobserver variability, and accelerate the diagnostic process. This review underscores the transformative role of AI and radiomics in lung cancer management, highlighting their synergy in advancing precision oncology. As ongoing research continues to refine these methodologies, the future of lung cancer care is poised for significant advancements, offering improved diagnostic accuracy, personalized therapies, and better patient outcomes.

Background: Major diagnostic and therapeutic changes led to the implementation of the ‘lung cancer diagnosis in small biopsies and cytology specimens’ concept in the WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart in 2015. Touch imprints are an established technique in cytology that provides a rapid and minimally invasive method for morphological diagnoses of clinical specimens, accurate subtyping, and molecular characterizations of malignancies. The extended diagnostic requirements from the increasingly limited material provided by minimally invasive biopsy techniques pose major challenges for pathology. Recognizing the relevant features and potential pitfalls is essential for cytologists to avoid misinterpretation. Materials and Methods: A retrospective analysis of endoscopic and surgical biopsy diagnostics was performed on 717 patients (303 women and 414 men; average age of 66.9 years) with clinically suspicious tumor findings at the LungenClinic Grosshansdorf in 2020. A total of 1363 cytological samples were obtained pre-therapeutically from 986 distinct biopsies covering 330 surgically and 656 endoscopically examined pulmonary, mediastinal, and bronchial regions. These samples were then compared with the histological diagnoses that were critical for determining the final therapy. Results: Out of a total of 656 endoscopically examined cases, 322 were classified as malignant, 308 as benign, and 26 as undetermined. While touch imprints and histological analysis separately achieved specificity values of 95.4% and 98.8%, both methods showed sensitivity values of 82.1% and 86.5%, respectively. In contrast, combining the two methods improved the sensitivity by 8 percentage points to 94.6%. Out of 330 cases of surgically examined samples, 137 were malignant, 190 were benign, and 3 were undetermined. The specificity of the morphological examinations for these samples was comparably high at 97.9% and 100%, respectively. In this surgical setting, touch imprints alone achieved a sensitivity of 75.9% (n = 104/137 cases), with a specificity of 97.9% (n = 186/190 cases). The outcome of the histological approach alone and in combination with touch imprints reached a sensitivity of 96.4% (n = 132/137 cases). Conclusions: Cytology and histology achieved comparably high sensitivity and specificity values on small biopsies. Under optimal conditions for morphological analysis in a surgical setting, the sensitivity of cytology for detecting malignant tumors was only 6 percentage points lower compared with the clinical endoscopic setting. A combined approach of cytologic–histologic evaluation for endoscopically examined specimens significantly increased the sensitivity by approximately 8% compared with the surgical setting (p < 0.003).